Czajkowska-Kośnik Anna, Misztalewska-Turkowicz Iwona, Wilczewska Agnieszka Zofia, Basa Anna, Winnicka Katarzyna
Department of Pharmaceutical Technology, Medical University of Białystok, Mickiewicza 2c, 15-222 Białystok, Poland.
Department of Organic Chemistry, University of Białystok, Ciołkowskiego 1K, 15-245 Białystok, Poland.
Materials (Basel). 2024 Aug 7;17(16):3923. doi: 10.3390/ma17163923.
Poor water solubility of drugs is a limiting factor for their bioavailability and pharmacological activity. Many approaches are known to improve drug solubility, and among them, the physical method, solid dispersions (SDs), is applied. SDs are physical mixtures of a drug and a carrier, sometimes with the addition of a surfactant, which can be obtained by milling, cryomilling, spray-drying, or lyophilization processes. In this study, solid dispersions with etodolac (ETD-SDs) were prepared by the milling method using different carriers, such as hypromellose, polyvinylpyrrolidone, copovidone, urea, and mannitol. Solubility studies, dissolution tests, morphological assessment, thermal analysis, and FTIR imaging were applied to evaluate the SD properties. It was shown that the ball-milling process can be applied to obtain SDs with ETD. All designed ETD-SDs were characterized by higher water solubility and a faster dissolution rate compared to unprocessed ETD. SDs with amorphous carriers (HPMC, PVP, and PVP/VA) provided greater ETD solubility than dispersions with crystalline features (urea and mannitol). FTIR spectra confirmed the compatibility of ETD with tested carriers.
药物的低水溶性是其生物利用度和药理活性的限制因素。已知有许多方法可提高药物溶解度，其中物理方法——固体分散体（SDs）被应用。固体分散体是药物与载体的物理混合物，有时还会添加表面活性剂，可通过研磨、低温研磨、喷雾干燥或冻干工艺获得。在本研究中，采用研磨法使用不同载体（如羟丙甲纤维素、聚乙烯吡咯烷酮、共聚维酮、尿素和甘露醇）制备依托度酸固体分散体（ETD-SDs）。通过溶解度研究、溶出度试验、形态评估、热分析和傅里叶变换红外光谱成像来评估固体分散体的性质。结果表明，球磨工艺可用于制备含依托度酸的固体分散体。与未处理的依托度酸相比，所有设计的ETD-SDs均具有更高的水溶性和更快的溶出速率。含无定形载体（羟丙甲纤维素、聚乙烯吡咯烷酮和聚乙烯吡咯烷酮/醋酸乙烯酯）的固体分散体比具有结晶特性的分散体（尿素和甘露醇）具有更高的依托度酸溶解度。傅里叶变换红外光谱证实了依托度酸与测试载体的相容性。
